Examining the effects of prenatal alcohol exposure on performance of the sustained attention to response task in children with an FASD.

Prenatal alcohol exposure (PAE), the leading known cause of childhood developmental disability, has long-lasting effects extending throughout the lifespan. It is well documented that children prenatally exposed to alcohol have difficulties inhibiting behavior and sustaining attention. Thus, the Sustained Attention to Response Task (SART), a Go/No-go paradigm, is especially well suited to assess the behavioral and neural functioning characteristics of children with PAE. In this study, we utilized neuropsychological assessment, parent/guardian questionnaires, and magnetoencephalography during SART random and fixed orders to assess characteristics of children 8-12 years old prenatally exposed to alcohol compared to typically developing children. Compared to neurotypical control children, children with a Fetal Alcohol Spectrum Disorder (FASD) diagnosis had significantly decreased performance on neuropsychological measures, had deficiencies in task-based performance, were rated as having increased Attention-Deficit/Hyperactivity Disorder (ADHD) behaviors and as having lower cognitive functioning by their caretakers, and had decreased peak amplitudes in Broadmann's Area 44 (BA44) during SART. Further, MEG peak amplitude in BA44 was found to be significantly associated with neuropsychological test results, parent/guardian questionnaires, and task-based performance such that decreased amplitude was associated with poorer performance. In exploratory analyses, we also found significant correlations between total cortical volume and MEG peak amplitude indicating that the reduced amplitude is likely related in part to reduced overall brain volume often reported in children with PAE. These findings show that children 8-12 years old with an FASD diagnosis have decreased amplitudes in BA44 during SART random order, and that these deficits are associated with multiple behavioral measures.

Prospective validation of a new airway management algorithm and predictive features of intubation difficulty.

BACKGROUND: Some patients have features that indicate possible difficulty with direct laryngoscopy for tracheal intubation. Prediction of the likely outcome and selection of patients for an enhanced management algorithm would reduce the possible harm from failed intubation attempts. METHODS: Adult elective patients were assessed for seven features associated with difficult direct laryngoscopy, ranked in difficulty from 0 to 3. For a patient with at least one Class 3 feature, or two or more features of class 1 or higher, the enhanced management used a channelled videolaryngoscope Airtraq™ instead of a Macintosh laryngoscope. A long flexible angulated stylet and a flexible fibrescope would be used as the second and third steps. For patients with lesser difficulty scores, a Macintosh laryngoscope was used. Outcomes of enhanced management were analysed. Logistic regression and Random Forest algorithm, using the ranks of the predictive features, were used to predict difficulty during enhanced management. RESULTS: We prospectively studied 16 695 patients. We selected 1501 (9%) for enhanced management, and tracheal intubation was successful in all of them. Of these, 73% were intubated in less than 30 s, and only 4.5% required more than 4 min for intubation. Progression to the second and third steps of enhanced management was predicted by restriction of mouth opening and reduced cervical spine mobility. CONCLUSIONS: An enhanced management algorithm allowed successful tracheal intubation of all patients with anticipated difficult laryngoscopy. The need to combine the use of a stylet and a fibrescope with the Airtraq™ could be predicted with a high degree of certainty.

Coagulase-negative staphylococci are associated to the mild inflammatory pattern of healthcare-associated meningitis: a retrospective study.

The epidemiology of healthcare-associated meningitis (HAM) is dominated by commensal bacteria from the skin, as coagulase-negative staphylococci (CoNS). We hypothesized that the pauci-symptomatic and mild inflammatory patterns of HAM are related to the low pathogenic state of CoNS. Our aim was to describe clinical and biological features of CoNS HAM, compared to other HAM. All consecutive patients with HAM admitted in our hospital were retrospectively included from 2007 to 2014. HAM due to CoNS were compared to HAM caused by other bacteria (controls) for clinical and laboratory patterns. Seventy-one cases of HAM were included, comprising 18 CoNS and 53 controls. Patients were not different in terms of baseline characteristics. CoNS HAM occurred later after the last surgery than controls (17 vs. 12 days, p = 0.029) and had higher Glasgow Coma Scale (GCS) score (14 vs. 13, p = 0.038). Cerebrospinal fluid (CSF) analysis revealed a lower pleocytosis (25 vs. 1340/mm3, p < 0.001), a higher glucose level (3.75 vs. 0.8 mmol/L, p < 0.001), and a lower protein level (744 vs. 1751 mg/L, p < 0.001) in the CoNS group than in the control group, respectively. HAM due to CoNS was significantly less symptomatic and less inflammatory than HAM due to other bacteria.

Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis.

BACKGROUND: The role of vasopressors in trauma-related haemorrhagic shock (HS) remains a matter of debate. They are part of the most recent European recommendations on the management of HS and are regularly used in France. We assessed the effect of early administration of noradrenaline in 24 h mortality of trauma patients in HS, using a propensity-score analysis. METHODS: The study included patients from a multicentre prospective regional trauma registry. HS was defined as transfusion of ≥4 erythrocyte-concentrate units during the first 6 h. Patients with a Glasgow coma scale=3 and pre-hospital traumatic cardiac arrest were excluded. The main outcome measure was in-hospital mortality. The explicative and adjustment variables for the outcome and treatment allocation were predetermined by a Delphi method. The in-hospital mortality of patients with and without early administration of noradrenaline was compared in a propensity-score model, including all predetermined variables. RESULTS: Of 7141 patients in the registry in the study period, 6353 were screened and 518 patients in HS (201 with early noradrenaline use and 317 without) were included and analysed. After propensity-score matching, 100 patients remained in each group, and the hazard-ratio mortality was 0.95 (95% confidence interval: 0.45-2.01; P=0.69). CONCLUSIONS: The results of the present study suggest that noradrenaline use in the early phase of traumatic HS does not seem to affect mortality adversely. This observation supports a rationale for equipoise in favour of a prospective trial of the use of vasopressors in HS after trauma.

Cerebral small vessel disease and renal function: systematic review and meta-analysis.

BACKGROUND: The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure. METHODS: We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation. RESULTS: After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the presence of SVD was associated with an increased risk of renal impairment (whether proteinuria or reduced eGFR) OR 2.33 (95% CI 1.80-3.01), when compared to those without SVD. After adjustment for age and hypertension, 15/21 studies still reported a significant association between renal impairment and SVD. CONCLUSION: We found no specific association between renal impairment and lacunar stroke, but we did find that in individuals who had not had a stroke, having more SVD features on imaging was associated with a worse renal function, which remained significant after controlling for hypertension. However, this finding does not exclude a powerful co-associate effect of age or vascular risk factor exposure. Future research should subtype lacunar stroke sensitively and control for major risk factors.

Anaesthesia and intensive care management of face transplantation.

The face-grafting techniques are innovative and highly complex, requiring well-defined organization of all the teams involved. Subsequent to the first report in France in 2005, there have been 17 facial allograft transplantations performed worldwide. We describe anaesthesia and postoperative management, and the problems encountered, during the course of seven facial composite tissue grafts performed between 2007 and 2011 in our hospital. The reasons for transplantation were ballistic trauma in four patients, extensive neurofibromatosis in two patients, and severe burns in one patient. Anaesthesia for this long procedure involves advanced planning for airway management, vascular access, technique of anaesthesia, and fluid management. Preparation and grafting phases were highly haemorrhagic (>one blood volume), requiring massive transfusion. Median (range) volumes given for packed red cell (PRC) and fresh-frozen plasma (FFP) were 64.2 ml kg(-1) (35.5-227.5) and 46.2 ml kg(-1) (6.3-173.7), respectively. Blood loss quantification was difficult because of diffuse bleeding to the drapes. The management of patients with neurofibromatosis or burns involving the whole face was more difficult and haemorrhagic than the patients with lower face transplantation. Average surgical duration was 19.1 h (15-28 h). Postoperative severe graft oedema was present in most patients. Most patients encountered complications in ICU, such as renal insufficiency, acute respiratory distress syndrome, and jugular thrombosis. Opportunistic bacterial infections were a feature during the postoperative period in these highly immunosuppressed patients.

Effect of age on the comparability of bispectral and state entropy indices during the maintenance of propofol-sufentanil anaesthesia.

BACKGROUND: Manufacturers recommend maintaining anaesthesia at a bispectral index (BIS) or state entropy (SE) index value between 40 and 60. METHODS: We prospectively studied 102 patients receiving propofol-sufentanil anaesthesia administered by anaesthetists blinded to these indices. The main endpoint was crude agreement (P(0)), defined as the proportion of agreement between BIS and SE index among three categories: <40, between 40 and 60, and >60. Discrepancies in recommendation (DR) were also considered. A DR is type 1 if BIS or SE is <40, while the other is simultaneously >60. A DR is type 2 when BIS and SE index values are on different sides of a threshold (40 or 60) with three subtypes according to the magnitude of their difference. A linear multiple regression was performed to identify covariates that are independently associated with P(0). RESULTS: In total, 12 147 pairs of values were studied. P(0) was 59.9 (24.5%) [mean (sd)]. Thirty-three patients presented more than 50% discordant pairs and only seven patients presented more than 95% concordant pairs. Type 1 DR occurred in only 1.1% of all the pairs. The median (inter-quartile range) number of type 2 DR varied from 5 (3-8) to 2 (1-3) according to the degree of difference. Multivariate analysis showed that age (P=0.0004) and electrode position (P=0.0084) were independently associated with P(0). An increase in the age of 10 yr decreases P(0) by 5%. CONCLUSIONS: The agreement between BIS and SE indices is moderate and deteriorates as patients' age increases. This study cannot determine which index is best adapted for elderly patients. Additional work comparing both indices with raw EEG traces is warranted.

Examining the effects of prenatal alcohol exposure on corticothalamic connectivity: A multimodal neuroimaging study in children.

Children with a fetal alcohol spectrum disorder (FASD) experience a range of cognitive and behavioral effects. Prior studies have demonstrated white matter changes in children with FASD relative to typically developing controls (TDC) and these changes relate to behavior. Our prior MEG study (Candelaria-Cook et al. 2020) demonstrated reduced alpha oscillations during rest in FASD relative to TDC and alpha power is correlated with behavior. However, little is known about how brain structure influences brain function. We hypothesized that alpha power was related to corticothalamic connectivity. Children 8-13 years of age (TDC: N = 25, FASD: N = 24) underwent rest MEG with eyes open or closed and MRI to collect structural and diffusion tensor imaging data. MEG spectral analysis was performed for sensor and source data. We estimated mean fractional anisotropy in regions of interest (ROIs) that included the corticothalamic tracts. The FASD group had reduced mean FA in three of the corticothalamic ROIs. FA in these tracts was significantly correlated with alpha power at the sensor and source level. The results support the hypothesis that integrity of the corticothalamic tracts influences cortical alpha power. Further research is needed to understand how brain structure and function influence behavior.

French recommendations for the management of patients with spinal cord injury or at risk of spinal cord injury.

OBJECTIVES: To update the French guidelines on the management of trauma patients with spinal cord injury or suspected spinal cord injury. DESIGN: A consensus committee of 27 experts was formed. A formal conflict-of-interest (COI) policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The committee studied twelve questions: (1) What are the indications and arrangements for spinal immobilisation? (2) What are the arrangements for pre-hospital orotracheal intubation? (3) What are the objectives of haemodynamic resuscitation during the lesion assessment, and during the first few days in hospital? (4) What is the best way to manage these patients to improve their long-term prognosis? (5) What is the place of corticosteroid therapy in the initial phase? (6) What are the indications for magnetic resonance imaging in the lesion assessment phase? (7) What is the optimal time for surgical management? (8) What are the best arrangements for orotracheal intubation in the hospital environment? (9) What are the specific conditions for weaning these patients from mechanical ventilation for? (10) What are the procedures for analgesic treatment of these patients? (11) What are the specific arrangements for installing and mobilising these patients? (12) What is the place of early intermittent bladder sampling in these patients? Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® Methodology. RESULTS: The experts' work synthesis and the application of the GRADE method resulted in 19 recommendations. Among the recommendations formalised, 2 have a high level of evidence (GRADE 1+/-) and 12 have a low level of evidence (GRADE 2+/-). For 5 recommendations, the GRADE method could not be applied, resulting in expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. CONCLUSIONS: There was significant agreement among experts on strong recommendations to improve practices for the management of patients with spinal cord injury.

Nitrogen-15: microbiological alteration of abundance.

The abundance of N(15) relative to N(14) is significantly altered during experiments in vitro in which nitrate and nitrite are microbiologically reduced to nitrogen gas. In all studies to date, N(14)O(3)-and N(14)O(2)-species have been preferentially reduced. This selectivity has a complex dependence on conditions in the medium. The results are not only relevant to natural variations in N(15) relative to N(14) but should be seriously considered during N(15) tracer studies in soils.

An outbreak of strangles associated with a novel genotype of Streptococcus equi subspecies equi in donkeys in China during 2018.

BACKGROUND: Strangles is a highly contagious respiratory disease of equids caused by the bacterium Streptococcus equi subspecies equi. OBJECTIVES: To identify the cause of an outbreak of strangles that occurred on donkey farms within the Shandong Province of China and determine the prevalence of the disease. STUDY DESIGN: Cross-sectional. METHODS: Samples were taken from clinically affected animals to measure the prevalence of strangles within the population of donkeys at six intensive farms in China and identify the SeM type of isolate recovered from affected animals. Diagnosis was confirmed by bacterial isolation, biochemical tests and PCR. Epidemiological data were analysed using Chi-square test and a Fisher's exact two-sided test. The SeM gene of S. equi isolates recovered from affected animals was determined and compared with the SeM database PubMLST-seM. RESULTS: In July and August 2018, an outbreak of strangles occurred on six donkey farms within the Shandong Province of China. The overall prevalence of disease within the different donkey herds was 13.4%. Younger animals were worst affected with 40.3% (83/206) of donkey foals aged under 1 year exhibiting clinical signs compared with 12.5% (191/1525) of donkeys aged one to 2 years and 3.8% (17/442) of donkeys over 2 years of age. Analysis of SeM sequencing data identified that the farms were affected by the same strain of S. equi, SD201807, which contains the novel 136 allele of SeM. MAIN LIMITATIONS: Healthy donkeys were not sampled in this study. CONCLUSIONS: The number of intensive donkey breeding farms in China has risen recently. The higher numbers of animals that are in closer proximity to one another raise the potential for the transmission of infectious diseases such as strangles. This is the first description of a strangles outbreak among donkey herds in China. The Summary is available in Chinese - see Supporting information.

A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications.

The molecular pathogenesis of pancreatic endocrine tumors is largely unknown. Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome. We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL. Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors. Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease.

Role of organic matter in framboidal pyrite oxidation.

An experimental system has been set up to investigate the reaction kinetics of framboidal pyrite oxidation in real, reactive acid sulfate soil assemblages. This study was undertaken to determine the degree to which pyrite oxidation rates are reduced by bacteriological reactions and organic matter, which both modify the net reaction mechanisms and compete for available oxygen. The results from these experimental runs not only confirm the role of organic matter in mitigating pyrite oxidation but indicate that at least initially, the acidity produced is consumed or otherwise ameliorated by parallel reactions. Tracking pH or [H+] in both a reactor and in soil does not accurately reflect reaction progress and may not correctly indicate the true level of risk. In comparison, the tracking of pyrite oxidation with the concentration of sulfate in solution is not affected by side reactions or precipitation and is therefore a better indicator for the rate of pyrite destruction.

Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors.

Only two tumor suppressor gene loci, one on 3p25 and the MEN1 gene on 11q13, have thus far been implicated in the pathogenesis of sporadic human pancreatic endocrine tumors (PETs). A genome-wide allelotyping study of 28 human PETs was undertaken to identify other potential tumor suppressor gene loci. In addition to those on chromosomes 3p and 11q, frequent allelic deletions were identified on 3q (32%), 11p (36%), 16p (36%), and 22q (29%). Finer deletion mapping studies localized the smallest regions of common deletion to 3q27, 11p13, and 16p12.3-13.11. Potential candidate genes at these loci include WT1 (11p13), TSC2 (16p13), and NF2 (22q12), but no known tumor suppressor gene localizes to 3q27. The mean fractional allelic loss among these human PETs is 0.126, and no correlation was observed between allelic loss and clinical parameters, including age, sex, hormonal subtype, and disease stage. These findings highlight novel locations of tumor suppressor gene loci that contribute to the pathogenesis of human PETs, and several of these on 3p, 3q, and 22q are syntenic with loci on mouse chromosomes 9 and 16 that are implicated in a murine transgenic model of PETs.

Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18.

Lymphomas arising in mucosa-associated lymphoid tissue (MALT) are indolent B-cell tumors that have a predilection for epithelial sites and often develop in a setting of chronic inflammation or autoimmunity. As many as 50% of low-grade MALT lymphomas contain an (11;18)(q21; q21) chromosomal translocation. Using fluorescence in situ hybridization, we have analyzed the position of recombination within chromosome 18 DNA in three examples of MALT lymphoma bearing this translocation. In all three cases, the breakpoint maps to DNA in BAC b357H2, covering about 150 kb of sequence. A previously undescribed, ubiquitously expressed gene, which we refer to as MALT1, was identified within this sequence and was found to be broken in one case for which we have definitively located the position of recombination between chromosomes 18 and 11. The sequence of this gene indicates the presence of two immunoglobulin-like C2 domains and a region of partial homology to caspases, suggesting a possible role for MALT1 in the regulation of apoptosis.

Polymicrobial septicemia associated with rhabdomyolysis, myoglobinuria, and acute renal failure.

Myoglobinuria and renal failure resulting from bacterial infection have only rarely been reported. To our knowledge, we describe the first reported case of polymicrobial septicemia resulting in rhabdomyolysis and myoglobinuric renal failure. Renal failure secondary to myoglobinuria has an excellent prognosis; in our patient, recovery was complete. The frequency of rhabdomyolysis, myoglobinuria, and renal failure in septicemia is unknown and can only be determined by an increased awareness of this potential complication of septicemia.

Infective endocarditis in a community hospital.

Recent reviews from major university centers of infective endocarditis have stressed an increase in unusual infections owing to virulent pathogens. This article compares the 40 episodes of infective endocarditis at a community hospital complex with the recent literature. It was observed that the majority of infecting microorganisms were penicillin-susceptible streptococci similar to those seen in the early antibiotic era. An older patient population was encountered, but overall mortality was low. Streptococcus bovis was a frequent cause of both natural and prosthetic valve infections. Symptoms lasting longer than two months were associated with vegetations demonstrated by echocardiography and high morbidity. Clinical features in this series that significantly correlated with a poor prognosis were height of fever at admission, the failure of fever to resolve within one week of appropriate therapy, the degree of peripheral leukocytosis, gross hematuria, and CNS signs. Conservative parenteral treatment closely monitored by serum bactericidal levels was employed. No relapses occurred among patients surviving initial therapy.

Overexpression of cyclin D1 occurs frequently in human pancreatic endocrine tumors.

The molecular pathogenesis of human pancreatic endocrine tumors (PETs) is poorly understood. Three independent animal models have pointed to the pivotal role of the G1/S cell cycle transition in pancreatic endocrine cell proliferation. We thus hypothesized that the cell cycle regulator cyclin D1 may contribute to the pathogenesis of human PETs. Overexpression of cyclin D1 was identified in 43% of cases, and no correlation was observed with clinical phenotype. The novel observation of frequent overexpression of cyclin D1 suggests that this established oncogene may be implicated in the pathogenesis of human PETs. The absence of detectable alterations in cyclin D1 genomic structure suggests that the mechanism for its oncogenic activation in PETs may be transcriptional or posttranscriptional.

Flow cytometric measurement of non-specific esterase activity.

alpha-Naphthyl acetate esterase (alpha-NAE) is primarily found in mononuclear phagocytes and may be used to distinguish them from other leucocytes. Conventional cytochemical techniques are subjective and may be difficult to interpret, especially with cells which express only low levels of activity. This has caused difficulties in the classification of non-lymphoblastic leukaemias. This paper describes the adaptation of a cytochemical assay for use with the flow cytometer. The alpha-NAE activity of peripheral blood mononuclear cells was examined and found to be associated with the expression of the surface antigen CD14. The reaction could be inhibited by sodium fluoride. A series of human cell lines were also compared for alpha-NAE activity. Distinct differences in staining observed between the cell lines correlated with the number of cell-associated granules observed under the microscope.